title: Erythropoiesis-stimulating agents increase the risk of acute stroke in patients with chronic kidney disease.
abstract: Erythropoiesis-stimulating agents (ESAs) are effective in ameliorating anemia in chronic kidney disease (CKD). A recent trial in diabetic patients with CKD, however, suggested a greater risk of stroke associated with full correction of anemia with ESAs. Using national Veterans Affairs data we performed a case-control study examining the association of incident ESA use with acute stroke in patients with estimated glomerular filtration rate < 60 cm³/min per 1.73 m² and outpatient hemoglobin <12 g/dl. Using diagnosis codes, we identified 2071 acute hospitalized stroke cases and matched them 1:5 with controls without stroke, resulting in 12,426 total patients for analysis. Conditional logistic regression was used to estimate the association of ESA use with stroke, adjusting for potential confounders. After multivariate adjustment, ESA use in 1026 patients was associated with greater odds of stroke (odds ratio 1.30). There was significant interaction between ESA use and cancer, with greater odds of stroke among ESA-treated cancer patients (odds ratio 1.85), but not in ESA-treated patients without cancer (odds ratio 1.07). ESA-treated patients with cancer received a median initial dose 2.5-4 times greater than ESA-treated patients without cancer, but pre-ESA hemoglobin and its rate of change did not differ between these groups. Hence, in a large national sample of anemic patients with CKD, ESA treatment was associated with an increased risk of acute stroke with the greatest effect among patients with cancer.
authors.affiliation: Department of Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA. sseliger@medicine.umaryland.edu
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Seliger
authors.forename: Amy D
authors.initials: AD
authors.lastname: Zhang
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Weir
authors.forename: Loreen
authors.initials: L
authors.lastname: Walker
authors.forename: Van Doren
authors.initials: VD
authors.lastname: Hsu
authors.forename: Afshin
authors.initials: A
authors.lastname: Parsa
authors.forename: Clarissa J
authors.initials: CJ
authors.lastname: Diamantidis
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Fink
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000097:blood / Q000188:drug therapy* / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002908:Chronic Disease; D015897:Comorbidity; D005260:Female; D005919:Glomerular Filtration Rate; D006397:Hematinics / Q000009:adverse effects*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000503:physiopathology; D007674:Kidney Diseases / Q000097:blood / Q000453:epidemiology* / Q000503:physiopathology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000453:epidemiology; D016017:Odds Ratio; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology*; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology; D014493:United States Department of Veterans Affairs
chemical_list: D015415:Biomarkers; D006397:Hematinics; D006454:Hemoglobins